The Alliance NCI Community Oncology Research Program (NCORP) Research Base conducts interventional and observational clinical trials as well as database analyses addressing important questions concerning cancer prevention, screening, symptom intervention, post-treatment surveillance/survivorship, quality of life and cancer care delivery. We place special emphasis upon issues affecting minority, underserved and elderly patient groups, and upon building strong collegial relationships with NCORP Community sites and Minority/Underserved Community sites. The Alliance for Clinical Trials in Oncology (Alliance), one of the five National Clinical Trials Network (NCTN) groups, serves as the coordinating center for the conduct of all NCORP Research Base trials. The Alliance members represent community practices and academic medical centers in approximately equal number, so the results of the trials broadly reflect the actual experience of patients across the United States. In order to improve our understanding of the biological basis of cancer risk and pre-malignant disease, biomarkers that detect pre-symptomatic newly diagnosed or recurrent malignancies, as well as the physiologic mechanisms of cancer-related symptoms and treatment-related toxicities, most of our clinical trials include translational research questions requiring the collection of tumor tissue, premalignant tissue samples, blood, or other human biospecimens. These biospecimens create an invaluable repository for understanding the associations between laboratory and clinical observations. The Alliance NCORP Research Base collaborates broadly with other NCORP Research Bases to enroll patients in trials, conduct translational studies, and share data and biospecimens for pooled analyses. We also collaborate broadly with other NCI-funded investigators and consortia, as well as investigators supported through non-NCI sources. Results of Alliance investigator efforts have resulted in more than 99 abstracts and manuscripts over the past five years, many resulting in significant beneficial changes in clinical practice. The scientific questions answered by the Alliance NCORP Research Base represent meaningful and innovative contributions to biomedical sciences, and can only be addressed through a publicly-funded research network.